The proposed complementary studies of normal and abnormal development are centered on the role of the maxillary process in primary and secondary palatal development and in developmental alterations leading to cleft palate (CP). Of the many environmental agents which can induce CP in experimental animals, vitamin A seems to have the most human relevance. Studies by the applicant have shown that alterations in dietary levels of vitamin A strikingly affect the frequency of CP in genetically susceptible mouse embryos. Work by the applicant and others indicates that vitamin A has a major effect on migrating cells and preliminary investigations indicate that extensive cellular migrations are involved in maxillary process formation. The proposed study utilizes the increasing understanding of the biochemical mechanism of action of vitamin A to analyze its teratogenicity. The conspicious maxillary deficiency produced by vitamin A in susceptible mouse strains is very similar to the oel mouse, a strain with a recessively inherited maxillary deficiency syndrome resembling Treacher Collins Syndrome. The manner in which the medial nasal process interacts with the lateral nasal and maxillary processes in primary palate formation is poorly understood. In a separate study in which diphenylhydantoin (DPH, Dilantin) is being used to produce cleft lip, lateral nasal process development is severely retarded. The interaction of deficient processes in embryos treated with either vitamin A or DPH will be compared. These experimental manipulations, should provide considerable information about the mechanisms involved in primary palate development. Scanning electron microscopy (SEM) will be used for detailed examination of morphological changes that occur in normally and abnormally developing embryos and fetuses. The majority of studies will be conducted using mouse models, though chick and subhuman primates will be studied so that comparisons may be made. The proposed morphological, histochemical, and autoradiographic study of vitamin A-induced developmental disturbances promises to provide an important link in understanding the relationship between genetic and environmental influences, specific cellular abnormalities, and facial malformations.